Project Summary/Abstract Glaucoma is a family of eye disorders which causes permanent vision loss. Glaucoma, in most cases, has no early symptoms and is detected when the nerve damage and vision loss is irreversible. If global projections hold by 2020 there will be 76 million people with glaucoma. Elevated intraocular pressure (IOP) is a major risk factor for glaucoma. Unfortunately, elevated IOP is not always predictive as some glaucoma patients have normal IOP, while other individuals with elevated IOP do not manifest the disease. Glaucoma detection and disease management is a significant challenge in the field and many clinical issues remain unsolved. One of the biggest issues is that the eyes of some patients look like they have glaucoma and don?t while others look like they don?t have glaucoma but in fact are in the early stages of the disease. The newest frontier in glaucoma research is investigation of how ocular proteins relate to vision loss. Identification of relationship between glaucoma, proteins and other molecules will set the stage for better diagnostic modalities, improved treatment strategies, blindness prevention and therefore, reduce the global health burden of this disease. Aqueous humor (AH) is a fluid which bathes nearly all structures in the front of the eye as it flows from its source at the ciliary body to its exit: the trabecular meshwork. Some AH proteins originate from the ciliary body simultaneously within the aqueous component. Others are picked up as the fluid circulates through and around healthy and unhealthy ocular tissues. This proposal aims to quantitatively analyze these AH proteins and determine the relationship between them and glaucomatous optic neuropathy. This fluid can be safely collected during cataract and glaucoma surgeries where it is usually discarded. We will collect medical, social and clinical data on consenting cataract and glaucoma surgical patients. Some clinical parameters will be obtained from state of the art instruments which produce high definition images of nerve layers and configurations. The proteins in the AH will be identified and quantified using the latest generation mass spectrometry and statistically compared to clinical data. Bioinformatics analyses will be performed to reveal the cellular functions associated with protein alterations. Based on these data we will develop statistical models in an effort to identify individuals at risk for optic neuropathy. We aim to use the protein data to help classify subtypes in the family of glaucoma. Finally, we will develop a publicly available internet accessible database of AH proteins which we will populate with our protein discoveries. This database may also become part of the backbone of an electronic repository to enable data integration across different scientific laboratories. This approach should allow global glaucoma investigations to proceed more effectively eventually reducing the burden of blindness.